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用于人工耳蜗炎症传感未来应用的分子印迹聚合物的电化学降解

Electrochemical Degradation of Molecularly Imprinted Polymers for Future Applications of Inflammation Sensing in Cochlear Implants.

作者信息

Nguyen Minh-Hai, Onken Adrian, Sündermann Jan, Shamsuyeva Madina, Singla Pankaj, Depuydt Tom, Peeters Marloes, Wagner Patrick, Bethmann Konrad, Körner Julia, Endres Hans-Josef, Lenarz Thomas, Doll Theodor

机构信息

Department of Otolaryngology and Cluster of Excellence "Hearing4all", Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.

Department of Chemical Safety and Toxicology, Fraunhofer Institute of Toxicology and Experimental Medicine ITEM, Nikolai-Fuchs-Straße 1, 30625 Hannover, Germany.

出版信息

ACS Omega. 2024 May 24;9(23):25223-25238. doi: 10.1021/acsomega.4c02906. eCollection 2024 Jun 11.

Abstract

After cochlear implant (CI) insertion, there is a possibility of postoperative inflammation, which may involve proinflammatory markers such as interleukin-6. Detecting this inflammation promptly is crucial for administering anti-inflammatory drugs, if required. One potential method for detecting inflammation is using molecular imprinted polymers (MIPs). These MIPs, which can be deposited on the CI electrode, provide readout employing impedance measurements, a feature already available on the CI circuit. MIPs designed for this purpose should possess biocompatibility, conductivity, and degradability. The degradability is crucial because there is a limitation on the number of electrodes available, and once the inflammation sensor degrades after the acute inflammation period, it should remain usable as a regular electrode. In this work, conductive poly(3,4-ethylenedioxythiophene) polystyrenesulfonate-based MIPs were synthesized against biotin as a surrogate target marker. Specific biotin binding with MIPs was determined before and after degradation using electrochemical impedance spectroscopy (EIS) and compared with the control nonimprinted polymers (NIPs). Subsequently, MIPs were electrochemically degraded by EIS with different potentials, wherein a potential dependence was observed. With decreasing potential, fewer dissolved polymers and more monomer molecules were detected in the solution in which degradation took place. At a potential of 0.205 V a negligible amount of dissolved polymer in addition to the dissolved monomer molecules was measured, which can be defined as the limiting potential. Below this potential, only dissolved monomer molecules are obtained, which enables renal clearance. Biocompatibility testing revealed that both the polymer and the solution with dissolved monomer molecules do not exceed the ISO 10993-5 cytotoxicity threshold. Based on these findings, we have developed conductive, biocompatible, and controllably degradable MIPs capable of detecting biotin. This research work paves the way for the advancement of CIs, where inflammation can be detected using molecular imprinting technology without compromising the stability and biosafety of the product.

摘要

人工耳蜗植入后,存在术后炎症的可能性,这可能涉及白细胞介素-6等促炎标志物。如果需要,及时检测这种炎症对于使用抗炎药物至关重要。一种检测炎症的潜在方法是使用分子印迹聚合物(MIP)。这些可以沉积在人工耳蜗电极上的MIP通过阻抗测量提供读数,这是人工耳蜗电路已具备的一项功能。为此目的设计的MIP应具有生物相容性、导电性和可降解性。可降解性至关重要,因为可用电极数量有限,并且一旦炎症传感器在急性炎症期后降解,它应仍可作为常规电极使用。在这项工作中,合成了以生物素作为替代目标标志物的基于导电聚(3,4-亚乙基二氧噻吩)聚苯乙烯磺酸盐的MIP。使用电化学阻抗谱(EIS)在降解前后测定MIP与生物素的特异性结合,并与对照非印迹聚合物(NIP)进行比较。随后,通过EIS在不同电位下对MIP进行电化学降解,观察到了电位依赖性。随着电位降低,在发生降解的溶液中检测到的溶解聚合物减少,单体分子增多。在0.205 V的电位下,除了溶解的单体分子外,测量到的溶解聚合物量可忽略不计,这可定义为极限电位。低于此电位,仅获得溶解的单体分子,这使得能够通过肾脏清除。生物相容性测试表明,聚合物和含有溶解单体分子的溶液均未超过ISO 10993-5细胞毒性阈值。基于这些发现,我们开发了能够检测生物素的导电、生物相容且可控降解的MIP。这项研究工作为人工耳蜗的发展铺平了道路,在人工耳蜗中可以使用分子印迹技术检测炎症,而不会损害产品的稳定性和生物安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e965/11170751/bda58ad9683a/ao4c02906_0001.jpg

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